Abstract
Introduction
Prior studies have shown that the gut microbiomes of Alzheimer’s Disease (AD) patients differ from unaffected individuals. Sleep and circadian rhythm disturbances are common in AD and often precede dementia symptoms. Gut microbiome alterations have also been observed in models of circadian disruption. Therefore, we hypothesized that altering the gut microbiome could improve sleep/circadian rhythms and cognition in an AD mouse model.
Methods
Mice were given a dietary polysaccharide, Modified Resistant Maltodextrin (MRM), as a 1% solution in the drinking water beginning at 2 months of age. 5xFAD and wild-type (WT) littermates were tested. Sleep-wake was recorded by EEG/EMG, memory consolidation was tested by the Object-Location Memory test, and beta amyloid deposition in the brain was assayed (dot blot). Composition of the gut microbiota was determined from amplicon sequencing of the 16s ribosomal RNA gene from fecal DNA.
Results
MRM treatment reduced dark (active)-phase sleep and the phase scattering of REM sleep in 5xFAD mice, indices of circadian consolidation. 6-month-old 5xFAD mice given plain water exhibited no 24hr retention of object location memory. However, MRM-treated 5xFAD mice demonstrated 24-hour memory, even at 12 months of age. Both improved memory and increased consolidation of sleep were also observed in WT mice. Two unclassified species of bacteria from the family Tannerellaceae were significantly increased in MRM-treated 5xFAD and WT mice. At 12 months of age, synaptic and neuronal loss become prominent in this AD model. However, the level of beta amyloid deposition in the brain was not significantly different between MRM and water control groups.
Conclusion
MRM treatment altered the gut microbiome, improved circadian timing of sleep and memory retention, but did not impact beta amyloid deposition in 5xFAD mice. Because these effects were also present in WT mice, MRM-induced microbiome changes may affect sleep and cognition independently from beta amyloid.
Support
Northwestern University Feinberg School of Medicine Center for Circadian and Sleep Medicine
0103 Novel Prebiotic Enhances Sleep-Wake Cycle and Memory Consolidation in 5xFAD Mice
